6ft7
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of CLK3 in complex with compound 8a== | |
| + | <StructureSection load='6ft7' size='340' side='right' caption='[[6ft7]], [[Resolution|resolution]] 2.02Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6ft7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FT7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FT7 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=E6Q:3-phenyl-1~{H}-pyrrolo[3,4-g]indol-8-one'>E6Q</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Dual-specificity_kinase Dual-specificity kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.12.1 2.7.12.1] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ft7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ft7 OCA], [http://pdbe.org/6ft7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ft7 RCSB], [http://www.ebi.ac.uk/pdbsum/6ft7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ft7 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CLK3_HUMAN CLK3_HUMAN]] Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.<ref>PMID:9637771</ref> <ref>PMID:19168442</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cdc2-like kinases (CLKs) represent a family of serine-threonine kinases involved in the regulation of splicing by phosphorylation of SR-proteins and other splicing factors. Although compounds acting against CLKs have been described, only a few show selectivity against dual-specificity tyrosine phosphorylation regulated-kinases (DYRKs). We here report a novel CLK inhibitor family based on a 6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one core scaffold. Within the series, 3-(3-chlorophenyl)-6,7-dihydropyrrolo[3,4-g]indol-8(1H)-one (KuWal151) was identified as inhibitor of CLK1, CLK2 and CLK4 with a high selectivity margin towards DYRK kinases. The compound displayed a potent antiproliferative activity in an array of cultured cancer cell lines. The X-ray structure analyses of three members of the new compound class co-crystallized with CLK proteins corroborated a molecular binding mode predicted by docking studies. | ||
| - | + | Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype.,Walter A, Chaikuad A, Helmer R, Loaec N, Preu L, Ott I, Knapp S, Meijer L, Kunick C PLoS One. 2018 May 3;13(5):e0196761. doi: 10.1371/journal.pone.0196761., eCollection 2018. PMID:29723265<ref>PMID:29723265</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6ft7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Dual-specificity kinase]] | ||
| + | [[Category: Arrowsmith, C H]] | ||
| + | [[Category: Bountra, C]] | ||
[[Category: Chaikuad, A]] | [[Category: Chaikuad, A]] | ||
| - | [[Category: | + | [[Category: Delft, F von]] |
| + | [[Category: Edwards, A M]] | ||
[[Category: Knapp, S]] | [[Category: Knapp, S]] | ||
| - | [[Category: Edwards, A.M]] | ||
| - | [[Category: Arrowsmith, C.H]] | ||
| - | [[Category: Structural Genomics Consortium (Sgc)]] | ||
| - | [[Category: Von Delft, F]] | ||
[[Category: Kunick, C]] | [[Category: Kunick, C]] | ||
| - | [[Category: | + | [[Category: Structural genomic]] |
| + | [[Category: Walter, A]] | ||
| + | [[Category: Clk]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Kinase]] | ||
| + | [[Category: Sgc]] | ||
| + | [[Category: Splicing kinase]] | ||
| + | [[Category: Transferase]] | ||
Current revision
Crystal structure of CLK3 in complex with compound 8a
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Categories: Dual-specificity kinase | Arrowsmith, C H | Bountra, C | Chaikuad, A | Delft, F von | Edwards, A M | Knapp, S | Kunick, C | Structural genomic | Walter, A | Clk | Inhibitor | Kinase | Sgc | Splicing kinase | Transferase
